Electrophoretic variants of the vitamin D-binding protein (DBP) have been associated with type 2 diabetes as well as with metabolic characteristics that predispose to type 2 diabetes in several populations. The Gc gene that encodes DBP maps to chromosome 4q12, a region that has recently been found to be potentially linked to plasma glucose and insulin concentrations in Pima Indians. Therefore, the gene that encodes DBP was analyzed as a candidate gene for our linkage findings in the Pima Indians. Sequence analysis of the coding exons identified two previously described missense polymorphisms at codons 416 and 420, which are the genetic basis for the three common electrophoretic variants of DBP (Gc1f, Gc1s, and Gc2). These variants in DBP were associated with differences in oral glucose tolerance in nondiabetic Pima Indians.